The objective of the proposed research is to determine the enzymes responsible for the reductive metabolism of aromatic nitrocompounds under physiological conditions as a means of understanding those processes controlling nitro reduction in vivo. Therefore, the metabolism of the carcinogenic aromatic nitro compounds C14-5-nitro-2-furaldehyde semicarbazone, formic acid 2-(4-(5-nitro-2-furyl)-2-C14-2 thiazolyl) hydrozide and 2-nitrofurazene-9-C14 will be studied in the perfused rat liver. The amount of covalent binding of C14 to macromolecules in the liver will be used as a measure of the reductive metabolism of the substrate to the highly reactive hydroxylamine. The following enzymes have been shown to be capable of nitro reductase activity in in vitro experiments: aldehyde oxidase, xanthine oxidase, DT diaphorase, cytochrome P-450, and NADPH - cytochrome c reductase. The nitro reductase activity of these enzymes under physiological conditions will be tested by comparing the amount of C14 covalently bound under the following experimental conditions to that in control experiments. (1) Addition of menadione, a specific inhibitor of aldehyde oxidase to the perfusate. (2) Addition of allopurinol - a specific inhibitor of xanthine oxidase to the perfusate. (3) Addition of dicoumarol, a specific DT diaphorase inhibitor, to the perfusate. (4) Perfusion of livers with decreased content of cytochrome P-450 by pretreatment of animals with CoCl2. (5) Perfusion of livers with increased levels of NADPH - cytochrome c reductase and cytochrome P-450 by pretreatment of rats with phenobarbital.